the role of new antiplatelet agents and antiplatelet testing · the role of new antiplatelet agents...

The Role of New Antiplatelet Agents and Antiplatelet Testing

Kathleen A. Lusk, Pharm.D., BCPS Department of Pharmacy Practice University of the Incarnate Word

Feik School of Pharmacy April 12, 2014

Financial Disclosures

• I have no financial disclosures to report.

Pharmacist Learning Objectives

• List the adverse effects, monitoring parameters, and contraindications for the available antiplatelet agents.

• Describe the role of the new antiplatelet agents in the treatment of ischemic heart disease.

• Discuss the role of antiplatelet testing and determine its potential place in therapy.

• Determine appropriate therapeutic recommendations for patients with platelet nonresponsiveness.

Technician Learning Objectives

• List the generic and brand names for the available antiplatelet agents.

• Identify the indications for the available antiplatelet agents.

• List the contraindications for the available antiplatelet agents.

Patient Case MM is a 85 yo female who presents to the ED complaining of chest pain that occurred while she was sleeping. She describes the chest pain as “tightness” in the center of her chest. The pain radiates to her left arm and back. She rates the pain as 9/10 . In the ED she is diagnosed with an NSTEMI and is taken to the cardiac catheterization lab for PCI with a DES.

PMH: HTN x 40 years (home BP 140-150s)

HLD x 35 years

CAD s/p PCI with DES to LAD (6 months ago)

GERD x 2 years

Meds: Aspirin 81 mg PO daily

Atorvastatin 40 mg PO daily

Clopidogrel 75 mg PO daily

Lisinopril 20 mg PO daily

Metoprolol succinate 50 mg PO daily

NTG 0.4 mg SL q5 minutes prn CP

Omeprazole 40 mg PO daily

Vitals: BP 170/98 mmHg HR 108 RR 23 Temp 35.2oC SaO2 94% (RA) Ht 166 cm Wt 65 kg

Platelet Biology

• Platelet = thrombocyte

• Normal range: 150,000-350,000 cells/µL

• Principle function: prevent bleeding

– Involved in hemostasis

– Ischemic complications in CV disease

N Engl J Med 2008. 359(9):938-49. Clinical Medicine: Cardiology 2009;3:77-91. Department of Biostatistics & Epidemiology: College of Public Health, OUHSC; 2007 [18 Feb 2011; 3 Mar 2014].

Plaque Rupture and Thrombus Formation

1. Disruption of endothelial lining

Blood vessels lined with endothelial cells

↓

Blood flow ± vascular trauma exposes endothelial lining

↓

Exposure of thrombogenic substances to the circulating blood

J Biol Chem 1992; 267:13795-813. N Engl J Med 2008. 359(9):938-49.


2. Platelet Adhesion

Plaque rupture exposes circulating platelets to

adhesive proteins

↓

Platelets bind to adhesive proteins



3. Platelet Activation/Secretion

TXA2 and ADP secreted by platelets

↓

Activation of secondary messenger system

↓

Stimulation of neighboring platelets

↓

Secretion of additional TXA2 and ADP



4. Platelet shape change

Loss of discoid shape

↓

Conformational change in the platelet GP IIb/IIIa receptor

↓

GP IIb/IIIa receptor exposed and active


Inactive Platelet

Activated Platelet

http://biomed.brown.edu/Courses/BI108/BI108_2005_Groups/10/webpages/plateletslink.htm


5. Platelet aggregation

Fibrinogen binds to GP IIb/IIIa receptors on platelets

↓

Thrombus growth


Harrison's Principles of Internal Medicine, 18e. New York: McGraw-Hill; 2012. http://www.nottingham.ac.uk/nursing/practice/resources/cardiology/acs/platelet.php

P2Y12 Inhibitors

• Ticlopidine (Ticlid®)

• Clopidogrel (Plavix®)

• Prasugrel (Effient®)

• Ticagrelor (Brilinta®)

Psychosomatic Medicine 2001; 62(3):326-36.

http://www.psychosomaticmedicine.org/content/62/3/326/F1.large.jpg

P2Y12 Inhibitors Clopidogrel Prasugrel Ticagrelor

Active metabolite 2-oxo-clopidogrel R-138727 AR-C12490XX

Onset of action 300-600 mg: 6 hours

600 mg: 2 hours 75 mg: 48 hours

30 minutes 180 mg: 30 minutes

Metabolism Hepatic via CYP450

2C19

Rapid intestinal and serum to inactive

intermediate

Hepatic via CYP450 to active metabolite

Hepatic via CYP 3A4/5

Peak effect (time to max IPA)

300-600 mg: 20-37% at 6 hours

75 mg: 50-60% at 5-7 days

60 mg: 41% at 30 min

78-84% at 4 hours

180 mg: 88% at 2 hours

Plavix [package insert]. Bridgewater, NJ: Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership;2013 December. Effient [package insert]. Eli Lilly and Co. Indianapolis, IN. 2012 November. Brilinta [package insert]. AstraZeneca LP. Wilmington, DE. 2013 March. J Am Coll Cardiol 2007;50: 1844-51. Eur Heart J 2006;27:1038-47.

P2Y12 Inhibitors Clopidogrel Prasugrel Ticagrelor

Loading dose 300-600 mg 60 mg 180 mg

Maintenance dose 75 mg daily 10 mg daily 90 mg BID

CI Active bleed Active bleed h/o stroke

Active bleed Hepatic impairment

Cautions CYP2C19 inhibitors Weight < 60 kg Age ≥ 75 years

Strong CYP 3A4 inducers/inhibitors ASA dose > 100 mg

ADRs Bleeding

Bleeding Hypertension

Headache Hyperlipidemia

Back pain

Bleeding Dyspnea

Ventricular pauses Bradycardia

Increased SCr Cough


P2Y12 Inhibitors

Clopidogrel Prasugrel Ticagrelor

Monitoring Bleeding: every office visit and daily by patient Hemoglobin/hematocrit: baseline, q6-12 months, if bleed suspected

Monitoring (drug specific)

--- ---

Uric acid Serum creatinine

Dyspnea Ventricular pauses

Cost (30 days) $208.80 $297.36 $293.27


TRITON-TIMI 38 Trial Population ACS + PCI (N=13,608)

Treatments Prasugrel 60 mg x 1, 10 mg daily Clopidogrel 300 mg x 1, 75 mg daily

1o endpoint/ Results

Composite: CV death, nonfatal MI, nonfatal stroke • Prasugrel 9.9% vs. clopidogrel 12.1% (p<0.001)

Safety endpoint/ Results

TIMI Major and Minor Bleeding • Prasugrel 5.0% vs. clopidogrel 3.8% (p=0.002)

Additional Safety Data

Previous stroke or TIA • More bleeding in patients with previous CVD and less benefit

> 75 years of age and weight < 60 kg • More bleeding in patients > 75 yo and < 60kg

Conclusion Prasugrel is a agent to consider; however, thorough patient assessment necessary.

N Engl J Med 2007. 357;20:2001-15.

TRILOGY ACS Trial

Population UA/NSTEMI without revascularization (N=9326)

Treatments Prasugrel 10 mg daily (>75 yo: 5 mg daily)

Clopidogrel 75 mg daily


Composite: CV death, MI, stroke • All patients: prasugrel 18.7% vs. clopidogrel 20.3% (p=0.45) • < 75 yo: prasugrel 13.9% vs. clopidogrel 16.0% (p=0.21)


GUSTO severe /life threatening bleeding and TIMI major bleeding • No difference between groups or in age > 75 yo

Conclusions Prasugrel provided no benefit over clopidogrel No difference in bleeding

N Engl J Med 2012. 367;14:1297-309.

PLATO Trial

Population ACS (N=18,624)

Treatments Ticagrelor 180 mg x 1, 90 mg BID

Clopidogrel 300-600 mg x 1, 75 mg daily


Composite: CV death, MI, stroke • Ticagrelor 9.8% vs. clopidogrel 11.7% (p<0.001)


Stent thrombosis (definite) • Ticagrelor 1.3% vs. clopidogrel 1.9% (p=0.009)


Major Bleeding • Ticagrelor 11.6% vs. clopidogrel 11.2% (p=0.43) ADRs more common with ticagrelor • Dyspnea (13.8%), bradycardia (4.4%), ↑ uric acid, ↑ SCr

Conclusions Ticagrelor is an agent to consider, but thorough patient assessment necessary.

N Engl J Med 2009. 361;11:1045-57.

Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with ACS

Int J Cardiol 2011. 150(3):325-31.

Population ACS receiving ticagrelor or prasugrel


Death, non-fatal MI, non-fatal stroke • No difference between groups


Definite/probable stent thrombosis • Lower with prasugrel (OR 0.64 (0.43-0.93), p=0.020)


TIMI major bleeding • Higher with prasugrel (OR 1.43 (1.10-1.85), p=0.007)

Conclusions Similar efficacy between ticagrelor and prasugrel Weigh risk vs. benefit of prasugrel in regards to stent thrombosis and bleeding

Antiplatelet Agent Nonresponsiveness

Clopidogrel “Resistance”

• Persistent platelet activation despite clopidogrel use

Cardiovasc Res 2009;84(2): 309-16. Thrombosis Research 2007;120: 311-21.

Laboratory Endogenous mechanism preventing clopidogrel from

exerting full antithrombotic effects (Platelet reactivity)

Clinical Ongoing thrombotic events despite clopidogrel

(Vascular events)

Clopidogrel “Resistance”

• Incomplete blockade of the P2Y12 receptor

– Residual post-treatment P2Y12 activity with IPA

• Numerous signaling pathways mediate thrombotic complications

J Am Coll Cardiol 2005;45: 1157-69. Cardiovasc Res 2009;84(2): 309-16. Thrombosis Research 2007;120: 311-21.

Nonresponsiveness = failure to inhibit target

Nonresponsiveness ≠ treatment failure

Treatment failure vascular event

Clopidogrel Nonresponsiveness

Study # of

patients Pop-

ulation Loading

dose Maintenance

dose Non-responsiveness

prevalence

Angiolillo, et al Thromb Res

2005;115:101-8. 48 PCI 300 mg 75 mg 44%

Gurbel, et al. Circulation

2003;107:2908-13. 92 PCI 300 mg 75 mg 31-35%

Jaremo, et al. J Intern Med

2002;252:233-8. 18 PCI 300 mg 75 mg 28%

Lepantalo, et al. Eur Heart J

2004;25:476-83. 50 PCI 300 mg 75 mg 40%

Lev El, et al. J Am Coll Cardiol

2006;47:476-83. 150 PCI 300 mg --- 24%

Clopidogrel Nonresponsiveness

Study # of

patients Pop-

ulation Loading

dose Maintenance

dose Non-responsiveness

prevalence

Mobely, et al. Am J Coll Cardiol

2004;93:456-8. 50 PCI 300 mg 75 mg 30%

Mueller, et al. Thromb Haemost

2003;89:783-7. 115 PCI 600 mg 75 mg 5-11%

Dziewierz, et al. J Am Coll Cardiol

2007;49(24):2312-7.

31 CAD 300 mg --- 23%

Matetzky, et al. Kardil Pol

2006;62:108-17. 60 STEMI 300 mg 75 mg 25%

Angiolillo, et al. Diabetes

2005;54:2430-5. 52 Diabetes 300 mg 75 mg

Diabetes: 38% No diabetes: 8%

Mechanism of Nonresponsiveness

• Reduction in bioavailability

• Drug interactions

• Enhance platelet turnover

• Variable platelet response

Reduction in Bioavailability

• Noncompliance

– CHD and CVA: 22% of patients noncompliant

– CVD: up to 38% noncompliant

• Inadequate dose

• Poor absorption

– Intestinal defect or disease

Clinical Medicine: Cardiology 2009;3: 77-91. Psychosomatic Medicine 2001; 62(3):326-36. Thrombosis Research 2007;120: 311-21.

Drug Interactions

• Hepatic conversion to active metabolite

• 2C19 inhibition prevents conversion to active metabolite

2C19 Clopidogrel 2-oxo-clopidogrel

Clinical Medicine: Cardiology 2009;3: 77-91. Thrombosis Research 2007;120: 311-21.

Enhanced Platelet Turnover

• Increased production in bone marrow

• Introduction of new platelets not exposed to antiplatelet agents

– Transfusions

• Cigarette smoking

Clinical Medicine: Cardiology 2009;3: 77-91.

Variable Platelet Response

• Interpatient variability in platelet response to clopidogrel

– 83% of individual variance in response to clopidogrel

• Genetic variability may lead to suboptimal platelet response

– Increased number of P2Y12 receptors

– Polymorphisms of platelet receptors

Psychosomatic Medicine 2001; 62(3):326-36. Thrombosis Research 2007;120: 311-21.

Clopidogrel CYP2C19 Polymorphisms

Metabolism Genotype

Frequency (%)

White African

American Chinese

Extensive CYP2C19 *1/*1

(wild type) 74 66 38

Immediate CYP2C19 *1/*2 CYP2C19 *1/*3

26 29 50

Poor CYP2C19 *2/*2 CYP2C19 *2/*3 CYP2C19 *3/*3

2 4 14

Annu Rev Pharmacol Toxicol 2001;41:815-50.

Clinical Effects of Nonresponsiveness

• High platelet reactivity may increase CV event risk

• Limited data linking nonresponsiveness to CV events

Study

# of patients

Treatment Population 1o

endpoint Clinical implication

Matetzky, et al. Circulation 2004.

109; 3171-5. 60

Clopidogrel 300 mg x 1, 75 mg daily

STEMI + PCI MACE CV events:

Reduced IPA

Geisler, et al. Eur Heart J 2006. 27;

2420-5. 363


Symptomatic CAD +

intervention CV death

Adequate response 2.9% vs. low

response 18.2% (p=0.006)

J Am Coll Cardiol 2007; 49 (24):

2312-7. 804


ACS + PCI with DES

Stent thromb-

osis

Responders 2.3% vs. nonresponders 8.6%

(p<0.001)

EXCELSIOR Trial

Population CAD + elective stent placement (N=802)

Treatments Clopidogrel 600 mg x 1, 75 mg daily


Composite: death, MI, or urgent target lesion revascularization


Composite: bleeding complications (TIMI major bleeding)

Conclusion Level of platelet aggregation before PCI in patients pre-treated with clopidogrel correlated with early outcome following procedure

J Am Coll Cardiol 2006; 48 (9): 1742-50.

1st Quartile (%)

2nd Quartile (%)

3rd Quartile (%)

4th Quartile (%)

P value

0.5 0.5 3.1 3.5 0.03

1st Quartile (%)

2nd Quartile (%)

3rd Quartile (%)

4th Quartile (%)

P value

1.4 1.0 1.0 0.5 0.83

Platelet Function Testing

Platelet Function Tests

• Single, standardized laboratory method lacking

• Prevalence of antiplatelet nonresponsiveness varies

– Laboratory method used

– Drug studied

– Dose prescribed

– Concomitant disease states

Clinical Medicine: Cardiology 2009;3: 77-91. Thrombosis Research 2007;120: 311-21.

Platelet Function Tests

• Light Transmittance Aggregometry (LTA)

• Vasodilator-stimulated phosphoprotein (VASP) phosphorylation analysis

• Multiple electrode platelet aggregometry (MEA)

• Platelet Function Assay

• Image Analysis, Monitoring, Platelet, Adhesion, Cone & Plate Technology (IMPACT-R)

• Plateletworks

• VerifyNow P2Y12 test

Light Transmittance Aggregometry

Vasodilator-Stimulated Phosphoprotein

Phosphorylation Analysis

Abbreviation LTA VASP Analysis

Point of Care No No

Measurement P2Y12 platelet receptor

inhibition P2Y12 platelet receptor

inhibition

Results Inhibition of platelet

aggregation (IPA) Index of platelet reactivity

to ADP (PRI %)

Whole Blood Use No No

Blood Sample Volume +++ ++

Use in Thrombocytopenia No Yes

Use with GP IIa/IIIb Inhibitors

No Yes

Studies Supporting Use +++ ++

Technical Skill Needed +++ +++

Speed of Results + +

Clinical Medicine: Cardiology 2009;3: 77-91. Biomarkers Med 2011;5(1):43-51. Thrombosis Research 2007;120: 311-21.

Multiple Electrode Platelet

Aggregometry

Platelet Function Assay

Image Analysis, Monitoring, Platelet,

Adhesion, Cone & Plate Technology

Abbreviation MEA PFA IMPACT-R Point of Care Yes Yes Yes

Measurement Platelet accumulation

on electrodes

Platelet adhesion and aggregation under

high shear conditions

Platelet adhesion and aggregation under

arterial flow

Results Arbitrary aggregation

units (AU) plotted against time

Time needed to form a clot to block a membrane slit

Percentage of the well surface covered

by platelet aggregates (percentage SC)

Whole Blood Use Yes Yes Yes Blood Sample Volume + + +

Use in Thrombocytopenia

No Yes No


Yes No No

Studies Supporting Use ++ ++ + Technical Skill Required ++ ++ ++

Speed of Results ++ +++ ++


Plateletworks VerifyNow P2Y12 Test

Abbreviation --- --- Point of Care Yes Yes

Measurement Single platelet

disappearance (SPD) ADP-induced platelet

aggregation

Results Percentage of IPA P2Y12 reaction units

(PRU) Whole Blood Use Yes Yes

Blood Sample Volume + + Use in

Thrombocytopenia No No


Yes No

Studies Supporting Use + ++ Technical Skill Required ++ +

Speed of Results +++ +++


VerifyNow P2Y12 Test

Advantages • Point-of-care

• Automated

• Cartridge-based

• Mobility

• Whole blood used

• Results in minutes

• NPV > 95%

• Meta-analysis concluded risk of CV events increases with higher PRU

Disadvantages

• Cannot be used in patients with recent exposure to GP IIb/IIIa inhibitors

• No validation in diverse populations

• Only small studies correlating results to CV events

Clinical Medicine: Cardiology 2009;3: 77-91. Biomarkers Med 2011;5(1):43-51.

POPULAR Trial

JAMA 2010; 303 (8): 754-62.

Population CAD + schedule PCI with BMS or DES (N=1069)

Treatments

Clopidogrel 300-600 mg x 1, 75 mg daily Platelet function tests: LTA, IMPACT-R, VerifyNow P2Y12, Plateletworks, Dade PFA collage/ADP test cartridge, Innovance PFA P2Y PFA 100


Composite: death, nonfatal MI, stent thrombosis, ischemic stroke Assessed platelet function tests’ ability to distinguish between patient with or without ischemic events • Able to distinguish between patients ± ischemic events

o LTA, VerifyNow P2Y12, Plateletworks, • Unable to discriminate between patients ± ischemic events

o IMPACT-R, Dade PFA collagen/ADP, Innovance PFA P2Y

Conclusions/ Comments

Only modest predictive accuracy of tests None of tests provided accurate prognostic information to identify low-risk patients at higher bleed risk following stent implantation

Overcoming Clopidogrel Nonresponsiveness

Treatment Options

• Increase doses

– Additional loading doses

– Higher daily doses

• Change the P2Y12 antagonist

– Prasugrel and ticagrelor proven efficacious • Not associated with genetic polymorphisms

– Cost difference

– Review side effect profiles and cautions/contraindications

N Eng J Med 2009;361:1045-57. N Engl J Med 2007;357(20):2001-15. N Engl J Med 2010;375:283-93. JACC Cardiovasc Interv 2010;3(10):1008-10.

GRAVITAS Trial

JAMA 2011; 305 (11): 1097-105.

Population Stable CAD or ACS s/p PCI (N=2800)

Treatments

Clopidogrel 300-600 mg x 1, 75 mg daily Patients assessed for presence of high on-treatment reactivity


Composite: CV death, nonfatal MI, stent thrombosis in patient with high on-treatment reactivity

High Dose Standard Dose

Loading dose 600 mg Placebo

Maintenance dose

150 mg daily 75 mg daily

High Dose (%) Standard Dose (%) p value

2.3 2.3 0.97

GRAVITAS Trial

JAMA 2011; 305 (11): 1097-105.


Composite: CV death, nonfatal MI, stent thrombosis in patients with standard clopidogrel dose ± high residual platelet activity


Moderate and severe bleeding

High On-Treatment Reactivity (%)

Without High On-Treatment Reactivity (%)

p value

2.3 1.4 0.20

High On-Treatment Reactivity (%)

Without High On-Treatment Reactivity (%)

High dose Standard dose p value Standard dose p value

1.4 2.3 0.10 1.2 0.12

GRAVITAS Trial

JAMA 2011; 305 (11): 1097-105.

Additional endpoint/ Results

Pharmacodynamics

Conclusions No benefit of high dose clopidogrel in patients with high on-treatment platelet reactivity

Questions remaining

Low event rate Clinical effect lacking Consider further dose increases? Level of platelet inhibition needed for efficacy?

PRU High Dose Standard Dose P value

30 days ↓ 80 PRU ↓ 37 PRU <0.001

6 months ↓ 85 PRU ↓ 44 PRU <0.001

BOCLA-Plan Trial

BMC Medicine 2011; 9 (3): 1-12.

Population Stable CAD or ACS s/p PCI (N=504)

Treatments

Clopidogrel 600 mg x 1, 75 mg daily Patients determined to be clopidogrel responder or nonresponder

Protocol

Steps 1 2

1 Clopidogrel 600 mg x 1,

150 mg daily Clopidogrel 600 mg x 1,

150 mg daily

2 Ticlopidine 500 mg x 1,

250 mg BID Prasugrel 60 mg x 1,

10 mg daily

3 ADP receptor defect

testing, then return to high dose clopidogrel

Prasugrel 20 mg daily

BOCLA-Plan Trial


Effective treatment

Conclusions Using “test and treat” strategy, the prevalence of clopidogrel low response can be significantly reduced

Questions remaining

What cut-off values should be used to determine nonresponsiveness Clinical effect lacking

BMC Medicine 2011; 9 (3): 1-12.

Clopidogrel Therapeutic Plan Effective Treatment (%)

Standard dose clopidogrel 69.2

High dose clopidogrel 69.0

Ticlopidine 12.7

Standard dose prasugrel 92.0

High dose prasugrel 100.0

TRIGGER-PCI Trial

Population Stable CAD with high on-treatment platelet reactivity with clopidogrel + PCI with DES (N=273)

Treatments Prasugrel 10 mg daily Clopidogrel 75 mg daily


Composite: CV death, MI • Prasugrel 0.0% vs. clopidogrel 0.5% (p=NE)

Additional endpoint/Results

Platelet reactivity (PRU) (3 months) • Prasugrel 245 80 vs. clopidogrel 249 241


Non-CABG related TIMI major bleeding • Prasugrel 1.4% vs. clopidogrel 0.5% (p=NE)

Conclusions Switching from clopidogrel to prasugrel increased level of effective platelet inhibition

Comments Discontinued early due to low incidence of 1o endpoint Clinical effect lacking

JACC 2012. 59;24:2159-64.

RESPOND Trial

Population Stable CAD (N=98)

Treatments

Clopidogrel 600 mg x 1, 75 mg daily Ticagrelor 180 mg x 1, 90 mg BID

Characterized as clopidogrel responder vs. nonresponder After 14 days, nonresponders switched groups and responders either continued current therapy or switched groups


Clopidogrel nonresponders who respond to ticagrelor • IPA higher in nonresponders treated with ticagrelor (p<0.05)

Additional outcomes

Platelet aggregation • Clopidogrel to ticagrelor 59.9% to ± 9% 35% ± 11% • Ticagrelor to clopidogrel 36% ± 14% 56% to ± 9% Platelet reactivity below cut points associated with ischemic risk • Ticagrelor 98-100% vs. clopidogrel 44-76%

Conclusions Ticagrelor provided greater platelet inhibition, but clinical benefit cannot be determined

Circulation 2010. 121:1188-99.

Randomized Assessment of Ticagrelor vs. Prasugrel Antiplatelet Effects in Patients with Diabetes

Population Type 2 diabetes + ACS + PCI with DES (N=30)

Treatments Ticagrelor 90 mg BID Prasugrel 10 mg daily

After 15 days, patients switched to opposite group


Platelet reactivity (PRU) • Ticagrelor 45.2 vs. prasugrel 80.8 (p=0.001)


High platelet reactivity (PRU > 230 PRU) • Ticagrelor 0% vs. prasugrel 3.3% (p=1.0)

Additional outcomes

No major bleeds or MACE occurred in either group

Conclusions Ticagrelor provided greater platelet inhibition, but clinical benefit cannot be determined

Diabetes Care 2013. 36:2211-6.

Summary

• P2Y12-mediated platelet reactivity is a risk factor for CV events

• Currently no large trial has found that on-treatment platelet reactivity is a modifiable risk factor

• Current strength of platelet function testing lies with its use to predict patient risk

• Greater and more consistent P2Y12 inhibition seems promising

– Antiplatelet regimens that improve IPA


Summary

• Evidence for tailoring antiplatelet regimens for high on-treatment reactivity

– Pharmacodynamic studies

– Small, nonrandomized clinical trials

• Questions remaining

– How does laboratory effects translate to clinical effects


Review Questions

1. True/False. Clopidogrel nonresponsiveness increases a patient’s risk of CV events.

a. True

b. False

2. True/False. Clopidogrel nonresponsiveness is synonymous with treatment failure.

a. True

b. False

Patient Case MM is a 85 yo female who presents to the ED complaining of chest pain that occurred while she was sleeping. She describes the chest pain as “tightness” in the center of her chest. The pain radiates to her left arm and back. She rates the pain as 9/10 . In the ED she is diagnosed with an NSTEMI and is taken to the cardiac catheterization lab for PCI with a DES.

PMH: HTN x 40 years (home BP 140-150s)

HLD x 35 years

CAD s/p PCI with DES to LAD (6 months ago)

GERD x 2 years

Meds: Aspirin 81 mg PO daily

Atorvastatin 40 mg PO daily

Clopidogrel 75 mg PO daily

Lisinopril 20 mg PO daily

Metoprolol succinate 50 mg PO daily

NTG 0.4 mg SL q5 minutes prn CP

Omeprazole 40 mg PO daily

Vitals: BP 170/98 mmHg HR 108 RR 23 Temp 35.2oC SaO2 94% (RA) Ht 166 cm Wt 65 kg

Patient Case

1. Which of the following platelet function test would be most appropriate for use in this patient?

a. IMPACT-R

b. Innovance PFA P2Y

c. VerifyNow P2Y12 test

d. None of the above

2. Which of the following regimens is most appropriate for this patient to prevent future CV events?

a. Clopidogrel 600 mg x 1, then 75 mg daily

b. Clopidogrel 600 mg x 1, then 150 mg daily

c. Prasugrel 60 mg x 1, then 10 mg daily

d. Ticagrelor 180 mg x 1, then 90 mg BID

The Role of New Antiplatelet Agents and Antiplatelet Testing

Kathleen A. Lusk, Pharm.D., BCPS Department of Pharmacy Practice University of the Incarnate Word

Feik School of Pharmacy April 12, 2014

the role of new antiplatelet agents and antiplatelet testing · the role of new antiplatelet agents...

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